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Biomedical subjects

P Vague

Publications and source records attributed to P Vague.

At least 73 records · Page 4Linked to original sources
PubMed1996

Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Adipocytes↗
PubMed1996

Erythrocyte Na(+)-K(+)-ATPase activity, metabolic control, and neuropathy in IDDM patients.

OBJECTIVE: To study the relationship among red blood cell Na(+)-K(+)-ATPase activity, metabolic control, and diabetic neuropathy. RESEARCH DESIGN AND METHODS: Na(+)-K(+)-ATPase activity has been measured in the red cell membrane of 43 long-standing IDDM patients (duration of diabetes 17.5 +/- 2 years, mean +/- SE), with 20 of the patients presenting with peripheral neuropathy. There were 23 healthy subjects serving as the control group. RESULTS: Na(+)-K(+)-ATPase activity was significantly lower in diabetic patients than in healthy subjects (236.5 +/- 7.5 vs. 294 +/- 10 nmol P1 . mg protein-1 . h-1, P < 0.05). Among diabetic patients, Na+/K(+)-ATPase activity was not dependent on the degree of diabetic control, nor was it correlated with either fasting blood glucose (r = 0.16, NS) or HbA1 (r = 0.01, NS). Na(+)-K(+)-ATPase activity was lower in patients with neuropathy than in those without it (212 +/- 8.5 vs. 261 +/- 6.6, P < 0.05). Furthermore, in a subgroup of 20 patients, a positive correlation was observed between erythrocyte Na(+)-K(+)-ATPase activity and nerve conduction velocity in the peroneal (r = 0.558, P < 0.02) and tibial nerve (r = 0.528, P < 0.05). CONCLUSIONS: These results suggest that diabetes-induced Na(+)-K(+)-ATPase activity dysfunction could be implicated in the pathogenesis of human diabetic neuropathy and the electrophysiological abnormalities observed in these patients.

Adult↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1996

Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus.

Disturbances of the haemostatic system may favour the development of vascular damage and the final occlusion events in the progress of coronary heart disease (CHD). It has been shown recently in epidemiological studies, that increased concentration of several factors, mainly fibrinogen, factor VII, von Willebrand factor (vWF), and the fibrinolytic variables plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA), can be considered as risk factors for CHD. As morbidity and mortality through coronary atherosclerosis are higher in type 2 diabetic patients than in nondiabetic subjects and as insulin resistance represents a situation which favours the development of atherothrombosis, evaluation of the haemostatic factors which are recognized as risk factors may be interesting to consider in these situations. In fact, it has been shown that the fibrinolytic parameters PAI-1 and t-PA antigen are strongly related to the metabolic disorder of insulin resistance, whereas the link with fibrinogen, factor VII, and vWF remains weak. Many cross-sectional studies conducted in different populations have shown that PAI-1 and t-PA antigen (which represents t-PA/PAI-1 complexes) are strongly correlated with insulin, triglyceride, high-density lipoprotein (HDL) cholesterol, body mass index, walst-to-hip ratio and blood pressure, and that the improvement of insulin resistance improves in parallel the metabolic abnormalities and the concentration of the fibrinolytic parameters. Attempts at explaining the elevated PAI-1 and t-PA antigen levels in the insulin resistance syndrome have involved many clinical and in vitro studies, in which the role of insulin, insulin propeptides, very-low-density lipoprotein (VLDL) triglyceride, insulin resistance per se, glucose, and adipose tissue have successively been analysed and the main results of these studies are presented in this review. Due to recent experimental data from animal models of thrombosis, a pathogenic role of decreased fibrinolytic activity or increased PAI-1 levels can be proposed and could play a role in the development of vascular disease in subjects with Type 2 diabetes or insulin resistance.

Blood Coagulation Factors↗
PubMed1996

[The implantable insulin pump in the treatment of diabetes. Hopes and reality?].

Advantages and drawbacks of the treatment of insulin-dependent diabetes by intra-peritoneal administration of insulin through an implanted infusion system are presented. This review is based upon our personal studies and the french experience centralized by the EVADIAC group. Between 1989 and 1994, 312 insulin-dependent patients were implanted in France. The mean followed up was 36 +/- 1 months, allowing an experience of 660 patients years. The main benefit is an important reduction in the incidence of severe hypoglycemia falling down from 15 per cent patient years before implantation to 2.5 per cent after. Although the patients were previously treated by intensive insulin treatment and well controlled, mean glycated hemoglobin was slightly improved and the glycemic stability increased as evidenced by the reduction of standard deviation of glycemia. Life duration of the implanted system averaged 38 months excepted for incidents requiring an explantation. Although the frequency of incidents was non negligible, they were acceptable. Vigilance, as performed by EVADIAC group is still necessary. This point can be illustrated by a technical problem which appeared recently and was due to a poor compatibility between a new preparation of insulin and the ejection chamber of the pump. Intraperitoneal administration of insulin allows to obtain plasma insulin concentration through the day closer to the physiology than that obtained with subcutaneous insulin infusion. Blood levels of some proteins, mainly SHBG and IGF1, return to normal values. However, this mode of administration is associated in some cases with an important increase of the insulin antibody levels, increase which does not seem to have a deleterious metabolic effect, but has to be carefully evaluated on the long term.

Adult↗
PubMed1995

[Bradycardia during treatments of weight loss].

Sinus bradycardia was observed in 10 adolescents participating in a weight loss diet conducted in a health centre. The precise cause was assessed. The subject's age ranged from 10 to 15 years and weight loss ranged from 8 to 24 kg over a period ranging from 8 to 23 weeks. None of the subjects had taken drugs with a bradycardic effect and search for toxic agents in the blood and urine was negative in all cases. Infection was suggested since 8 of the 10 adolescents had a rhinopharyngitis a few weeks before the discovery of bradycardia. This cause was not retained due to the lack of any signs of infection or inflammation and negative virus serology. Nutritional status was therefore retained as the most likely cause in these adolescents who were eating a diet containing < or = 1350 kcal/day. This hypothesis was supported by the results of work reported in 1970 showing arrhythmia in very low calorie diets. The effect is essentially related to the biological value of proteins in the diet, its duration and the initial weight of the subjects. In addition bradycardia is frequently seen in subjects taking hypocaloric diets or with anorexia nervosa and should be considered as an adaptation to hypometabolism rather than a true heart disorder. Thus the biological value of the proteins and the mineral status should be taken into consideration during the course of low calorie diets, even though bradycardia is frequent and does not require a specific treatment. Therefore heart rate and decreasing rate of weight loss should be carefully followed during the course of low calorie diets.

Adolescent↗
PubMed1995

Immunogenicity of long-term intraperitoneal insulin administration with implantable programmable pumps. Metabolic consequences.

OBJECTIVE: To assess immunogenicity of intraperitoneal insulin infusion via implanted pumps by two methods and to evaluate the possible influence of an increased antibody level on metabolic and clinical parameters. RESEARCH DESIGN AND METHODS: We studied insulin antibody levels in 17 type I diabetic patients before and until 24 months after implantation of a programmable pump delivering insulin intraperitoneally. Antibody levels were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). They were correlated with HbA1c, insulin requirements, free insulin, and the incidence of hypoglycemia. RESULTS: Insulin antibodies increased as soon as the 3rd month after implantation. This increase was sustained throughout the study period (month 0, 25.4 +/- 16.2%; month 3, 41.2 +/- 23.5%; month 12, 45.9 +/- 26%; month 24, 48.7 +/- 25%). The data was correlated with the two assay methods (RIA and ELISA). Postimplantation level was correlated with preimplantation level, which could indicate a predictive value of the latter . No correlation was observed with any metabolic parameters, particularly the number of hypoglycemic episodes. CONCLUSIONS: Our results indicate that intraperitoneal insulin administration by implantable programmable pumps leads to an increase of insulin antibodies, which are probably high-affinity antibodies (recognized by both RIA and ELISA). This increase in insulin immunogenicity did not induce significant metabolic consequences, which is reassuring for the future of programmable insulin pumps.

Adult↗
PubMed1995

Hypofibrinolysis and the insulin resistance syndrome.

Atherothrombosis seems now to be the most appropriate term to describe the pathogenic events leading to the development of cardiovascular disease. An impaired fibrinolysis may not only contribute to and aggravate the tendency to thrombosis but fibrin deposit may also play a role in the development of the atherosclerotic plaque. Hypofibrinolysis is observed among obese subjects and it has been shown that an excess of plasminogen activator inhibitor 1 (PAI 1) the main regulator of the fibrinolytic system, is closely associated to other components of the insulin resistance syndrome, namely, excessive body weight, high waist to hip ratio, elevated blood pressure, hyperinsulinemia and hypertriglyceridemia. PAI 1 levels decrease with measures attempting at decreasing insulin resistance. However, the mechanisms leading to increased PAI 1 levels are still unknown. On the basis of epidemiological studies, and in vitro studies with PAI secreting cells such as hepatocytes or endothelial cells, insulin, insulin precursors, and lipoproteins, mainly VLDL, appear candidates for triggering this excessive secretion, but no definite answer has yet been found.

Coronary Disease↗
PubMed1995

[Evaluation of assay methods of glycohemoglobin: reference method and parameter].

In this paper, the characteristics of the analytical procedures allowing the measurement of glycated hemoglobin products are presented. With respect to their respective performances, the authors recommend the specific measurement of HbA1c and the more reliable procedure, high pressure liquid chromatography (HPLC).

Chemistry Techniques, Analytical↗
PubMed1994

Modulation defect of sodium pump evidenced in diabetic patients by a microcalorimetric study.

Sodium pump activity of intact erythrocytes in their own plasma was measured by microcalorimetry in 41 healthy subjects and 35 insulin-dependent diabetic patients. Results show that modulation of the sodium pump is altered in diabetic patients. Addition of insulin increases functioning of the Na(+)-K+ pump in controls but has no effect in diabetic patients. These subjects show a slower response of the Na(+)-K+ pump to the inhibitory effect of ouabain. Cross-incubation experiments suggest that these findings may be explained by the existence of a plasmatic factor that impairs the modulation of the sodium pump in diabetic patients.

Adult↗
PubMed1994

Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.

Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗